ABSTRACT Alzheimer's disease and related dementias (ADRD) affect millions of Americans. Persons living in rural areas face increased prevalence (OR=1.1) and incidence (OR=1.2) of ADRD compared to urban/suburban dwellers with increased disparities affecting health outcomes. Underlying factors that may increase ADRD risk and disparities in health outcomes include: poverty; low education; poor health literacy; poor nutrition; tobacco, alcohol and substance abuse; limited access to care (specialists, diagnostic testing); migrant or marginal immigration status; and non- and underinsurance. In addition to rurality, race and ethnicity may play a role in ADRD. African Americans are 2 times as likely and Hispanics are 1.5 times more likely than Whites to develop ADRD that may be due to different risk profiles, particularly vascular risks. These social, biologic, and genetic determinants increase risk for multiple chronic conditions associated with vascular contributions to cognitive impairment and dementia (VCID). We propose to study health disparities associated with ADRD and more specifically VCID in culturally heterogeneous older adults living in a rural setting compared with older adults living in an urban/suburban setting. Comparison populations reside either in the (a) western rural portion of Palm Beach County, FL (locally referred to as ?the Glades?) or (b) the more metropolitan and affluent coastal portion of Palm Beach County (locally referred to as ?the Coast?). The overall HYPOTHESIS is that rurality, combined with low SES, cultural characteristics, vascular risk factors, environment and lifestyle factors, and genetic traits synergistically increase the risk for ADRD and in particular VCID. These same factors contribute to disparities in health outcomes for rural populations compared to similar groups of older adults from urban/suburban communities. We propose these SPECIFIC AIMS: (1) Conduct a cross-sectional, population- based study of the Glades with phenotype and genotype of participants to determine the prevalence of ADRD/VCID; (2) Conduct a longitudinal study of individuals randomly selected from Aim 1 and compare to an age- and racial/ethnicity-matched sample of suburban/urban older adults recruited for longitudinal follow-up; (3) Evaluate cross-sectional relationships at baseline, 18mos, and 36mos between clinical, functional, psychosocial, genetic, and biomarker variables and cognitive performance for the cohort as a whole, and stratified by relevant biological variables; and (4) Model baseline and longitudinal clinical, functional, psychosocial, behavioral, genetic, and biomarker variables to predict cognitive impairment and rate of progression from normal cognition to MCI, and MCI to ADRD/VCID for the cohort as a whole, and stratified by relevant biological variables. Our short-term goals are to determine prevalence and profile of transition from normal aging to ADRD/VCID, in a rural population compared to urban/suburban settings; identify and characterize unique genetic and biomarker features; and explore social and biologic determinants of brain health. Our long-term goal is to reduce health disparities.